Iranian Journal of Basic Medical Sciences
·
2021
·
IF 2.699
Chuang Zhang,Suolin Li,Chi Sun,Lin Liu,Yanbin Fang,Xiaofeng Yang,Xingxin Pan,Ben Zhang
Objective(s): Vitexin, a natural flavonoid, is commonly found in many foods and traditional herbal medicines and has clear health benefits. However, the role of vitexin in cholestasis is presently unclear. This study investigated whether vitexin mitigated glycochenodeoxycholate (GCDC)-induced hepatocyte injury and further elucidated the underlying mechanisms. Materials and Methods: A cell counting kit-8 (CCK-8) assay was conducted to evaluate cell viability. The mitochondrial membrane potential (MMP, Δψm), reactive oxygen species (ROS) levels, and apoptosis rate of hepatocytes exposed to GCDC were detected by flow cytometry (FCM). We then measured the cytoprotective effects of vitexin against oxidative stress. The molecular signaling pathway was further investigated by using Western blotting and signaling pathway inhibitors. Results: Here, we showed that vitexin increased cell viability and reduced cell apoptosis, necroptosis, and oxidative stress in a dose-dependent manner in GCDC-treated hepatocytes. In addition, by using selective inhibitors, we further confirmed that inhibition of the JAK2/STAT3 pathway by vitexin was mediated by prolonged activation of Sirtuin 6 (SIRT6). Conclusion: Vitexin attenuated GCDC-induced hepatocyte injury via SIRT6 and the JAK2/STAT3 pathways.
研究领域:
药理学
·
肝病学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Nan Li,Ruiyan Wang,Wenwen Li,Qian Du,Zeyuan deng,Yawei Fan,Liufeng Zheng
Vitexin, which exists in various medicinal plants and food sources, has recently received increasing attention because of its anti-inflammatory properties. This study aims to identify the protein target of vitexin that ameliorates dextran sulfate sodium (DSS)-induced colitis. The results showed that vitexin not only alleviated the clinical symptoms and colonic damage in mice with DSS-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, ICAM, and VCAM) and enhanced the expression of barrier-associated proteins (ZO-1, Occludin, and E-cadherin). Based on tissue thermal proteome profiling (Tissue-TPP) and molecular docking, OLA1 was creatively identified as a potential protein target for vitexin. Further siRNA-mediated knockdown of the OLA1 gene in Caco-2 cells demonstrated the ability of OLA1 to increase Nrf2 protein expression and, thus, mediated the anti-inflammatory effects of vitexin. Interaction of the OLA1–vitexin complex with Keap1 protein to disrupt the Keap1-Nrf2 interaction may be required for activating Nrf2. Our findings revealed a novel role for OLA1 as a protein target of vitexin that contributes to its anti-inflammatory action by activating Nrf2, which may provide a promising molecular mechanism for novel therapeutic strategies to treat colitis and the associated systemic inflammation.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaoxian Hu,Peiye Wu,Yu Zhao,Yun Wang,Zhongrui Li,Chao Han
Photodynamic therapy (PDT) is a minimally invasive treatment technique that combines photosensitizers and light and can selectively exert cytotoxic effects on malignant tumor cells and prevent their metastasis. However, while PDT is effective, it also triggers a tumor cell integrated stress response (ISR) to produce cytoprotective stress granules (SGs), decreasing its therapeutic efficacy. In this study, we designed a nanodrug delivery system capable of inhibiting the ISR to enhance the antitumor effect of PDT. Specifically, the low-toxicity photosensitizer hypericin (HY) and the highly effective SGs inhibitor imatinib (IM) were encapsulated in the HY and IM nanoparticles (HINPs). HY converts oxygen into reactive oxygen species under light conditions, inducing the apoptosis of tumor cells but simultaneously induces the formation of SGs through the eukaryotic initiation factor-2α-dependent pathway, reducing tumor sensitivity to PDT. IM tightly binds to the SGs core protein Ras-GAP SH3 domain binding protein 1 (G3BP1), preventing G3BP1 from forming a complex with ubiquitin-associated protein 2-like protein to inhibit SGs formation; it also inhibits the ATF3/CHOP/GADD34/PP1 negative feedback regulatory signaling axis of ISR, further disrupting tumor cell ISR and enhancing the efficacy of HY PDT. Both in vivo and in vitro experiments confirmed that HINPs have potent antitumor activity, providing a way to improve the antitumor efficacy of PDT.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Mengting Ni,Xin Song,Junhui Pan,Deming Gong,Guowen Zhang
In this study, the antiglycation potential and mechanisms of vitexin were explored in vitro by multispectroscopy, microscope imaging, high-resolution mass spectrometry, and computational simulations. Vitexin was found to show much stronger antiglycation effects than aminoguanidine. The inhibition against the fluorescent advanced glycation end products was more than 80% at 500 μM vitexin in both bovine serum albumin (BSA)–fructose and BSA–methylglyoxal (MGO) models. Treated with 100 and 200 μM vitexin for 24 h, the contents of MGO were reduced to 4.97 and 0.2%, respectively, and only one vitexin–mono-MGO adduct was formed. LC–Orbitrap-MS/MS analysis showed that vitexin altered the glycated sites and reduced the glycation degree of some sites. The mechanisms of vitexin against protein glycation were mainly through BSA structural protection, MGO trapping, and alteration of glycation sites induced by interaction with BSA. These findings provided valuable information about the functional development of vitexin as a potential antiglycation agent.
研究领域:
生物化学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Ning-Na Yin,An-Jin Yang,Chun Wu,Hai-Yan Xiao,Yu-Ruo Guo,Nai-Yong Liu
In this study, we annotated 49 odorant-binding proteins (OBPs) in Papilio xuthus, with four novel genes and seven improved sequences. Expression profiles identified numerous OBPs in antennae or reproductive tissues. Using two antenna-enriched general OBPs (PxutGOBP1 and PxutGOBP2) as targets, we screened three key compounds by a reverse chemical ecology strategy. Of these, an oviposition stimulant vicenin-2 could strongly interact with PxutGOBP1, representing a dissociation constant (Ki) value of 10.34 ± 0.07 μM. Molecular simulations and site-directed mutagenesis revealed the importance of His66, Thr73, and Phe118 between PxutGOBP1 and vicenin-2 interactions. Two other compounds, an ordinary floral scent β-ionone and a widely used insecticide chlorpyrifos, exhibited high affinities to PxutGOBPs (Ki < 13 μM). Furthermore, two mutations His66Ala and Thr73Ala of PxutGOBP1 significantly reduced the binding to chlorpyrifos. Our study provides insights into the putative roles of PxutGOBPs in odorant perception and identifies key binding sites of PxutGOBP1 to vicenin-2 and chlorpyrifos.
研究领域:
昆虫学
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基因组学
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化学生态学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Zhi-ping Fu,Yi-ge Ying,Rui-yao Wang,Yu-qing Wang
Arrhythmias and sudden cardiac death (SCD) impose a significant burden. Their prevalence rises with age and is linked to gut dysbiosis. Our study aimed to determine whether aged gut microbiota affects arrhythmogenesis. Here, we demonstrated that arrhythmia susceptibility in aged mice could be transmitted to young mice using fecal microbiota transplantation (FMT). Mechanistically, increased intestinal reactive oxygen species (ROS) in aged mice reduced ion channel protein expression and promoted arrhythmias. Gut microbiota depletion by an antibiotic cocktail reduced ROS and arrhythmia in aged mice. Interestingly, oxidative stress in heart induced by hydrogen peroxide (H 2 O 2 ) increased arrhythmia. Moreover, aged gut microbiota could induce oxidative stress in young mice colon by gut microbiota metabolites transplantation. Vitexin could reduce aging and arrhythmia through OLA1-Nrf2 signaling pathway. Overall, our study demonstrated that the gut microbiota of aged mice reduced cardiac ion channel protein expression through systemic oxidative stress, thereby increased the risk of arrhythmias.
研究领域:
心脏病学
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微生物学
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衰老
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药理学
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产品关联
DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2024
·
IF 6.4
Qiuxiao Yang,Dingding Shi,Yanling Ren,Chao Yang,Hongxia Qu,Yueming Jiang,Taotao Li
Pericarp browning is a vital factor limiting postharvest life of litchi fruit. The influence of vitexin on pericarp browning as well as the related mechanisms in litchi fruit were investigated. Results demonstrated that 1 mM vitexin ameliorated pericarp browning when litchi fruit were stored at 25 °C. Meanwhile, vitexin blocked reactive oxygen species (ROS) production but increased the glutathione peroxidase activity, thereby playing a protective role in oxidative injury. Additionally, vitexin attenuated ATP content decline in relation to regulation of LcSnRK1 as well as LcbZIP1/3 expressions. Furthermore, vitexin regulated expression levels of autophagy-related genes. Finally, LcbZIP3 activated the expressions of LcATG2 and Lcbeclin-1-like protein based on dual-luciferase report (DLR) assay. This is the first report that confers vitexin-meditated protective role in delaying litchi pericarp browning that could be linked to its effects on autophagy particularly regulated via LcSnRK1a–LcbZIP1/3 signaling pathway. Vitexin treatment might be an effective approach to control postharvest senescence of fruit during storage.
研究领域:
植物科学
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采后生理学
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分子生物学
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产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 6
·1-9
·
IF 2.447
Yue-Yuan Chen,Xiao-Jie Yan,Xiao-Hua Jiang,Feng-Lai Lu,Xue-Rong Yang,Dian-Peng Li
Aberrant destruction of the articular extracellular matrix (ECM) has been considered to be one of the pathological features of osteoarthritis (OA) which results in chondrocyte changes and articular cartilage degeneration. The MAPK signaling pathway serves a key role by releasing cartilage‑degrading enzymes from OA chondrocytes. However, the use of MAPK inhibitors for OA is hindered by their potential long‑term toxicity. Vicenin 3 is one of the major components of the Jian‑Gu injection which is effective in the clinical treatment of OA. However, its potential impact on OA remain poorly understood. Therefore, the present study aimed to assess the effects of vicenin 3 on interleukin (IL)‑1β‑treated SW1353 chondrocytes, which mimic the microenvironment of OA. These chondrocytes were pretreated with vicenin 3 (0, 5 and 20 µM) for 1 h and subsequently stimulated with IL‑1β (10 ng/ml) for 24 h. Nitric oxide (NO) production was measured using the Griess reaction, whereas the production of prostaglandin E2 (PGE2), matrix metalloproteinases (MMPs), A disintegrin‑like and metalloproteinase with thrombospondin motifs (ADAMTSs), collagen type II and aggrecan were measured using ELISA. The mRNA expression of MMPs and ADAMTSs were measured using reverse transcription‑quantitative PCR. The protein expression levels of MAPK were measured using western blotting. Vicenin 3 was found to significantly inhibit IL‑1β‑induced production of NO and PGE. Increments in the expression levels of MMP‑1, MMP‑3, MMP‑13, ADAMTS‑4 and ADAMTS‑5 induced by IL‑1β, in addition to the IL‑1β‑induced degradation of collagen type II and aggrecan, were all reversed by vicenin 3 treatment. Furthermore, vicenin 3 suppressed IL‑1β‑stimulated MAPK activation, an effect that was similar to that exerted by SB203580, a well‑known p38 MAPK inhibitor. In conclusion, vicenin 3 may confer therapeutic potential similar to that of the p38 MAPK inhibitor for the treatment of OA.
研究领域:
药理学
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风湿病学
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细胞生物学
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DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 14
·期 1
·171-180
·
IF 6.317
Xinlin Chen,Ying Wu,Yucheng Gu,Jianguang Luo,Lingyi Kong
A great deal of attention has been paid to the seeds of Paeoniae lactiflora pall., an underutilized food resource, since its extract exhibits excellent α-glucosidase (GAA) inhibitory activity. In the present study, to gain further insight into this plant and find out potent GAA inhibitors, we established a novel ligand fishing strategy by introducing a competitive inhibitor as an indicator. After the successful establishment of this approach was verified by a series of methods, including kinetic assay, fluorescence determination, and HPLC, the newly developed ligand fishing method was applied to acquire potent GAA inhibitors from P. lactiflora seeds. Nine bioactive compounds were captured, and seven of them were identified as suffruticosol A, suffruticosol B, resveratrol, vitisin E, luteolin, trans-δ-viniferin, and ampelopsin E. The data of their GAA inhibitory activity demonstrated that these constituents were vigorously active against GAA with IC50 values of 1.67–30.47 μM, while such value of 1-DNJ was 228.77 μM. Among them, vitisin E and ampelopsin E were reported to show such inhibitory activity for the first time. Collectively, our findings provide valuable clues for the further utilization of P. lactiflora seeds as a functional food, and offer a new avenue for acquiring potent inhibitors from natural resources.
研究领域:
药理学
·
天然产物化学
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生物化学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2023
·Vol. 18
·期 4
·045005
·
IF 4
Jian Zhang,Xiaoxiao Li,Xiaoli Xia,Michael Adu-Frimpong,Xinyi Shen,Qing He,Wanjing Rong,Feng Shi,Xia Cao,Hao Ji,Elmurat Toreniyazov,Qilong Wang,Jiangnan Yu,Ximing Xu
In this regard, we developed vitexin (Vi)-loaded D-ɑ-tocopherol polyethylene glycol succinate, polyvinylpyrrolidone K30 and sodium cholate mixed micelles (Vi-MMs) mainly for improving oral bioavailability and enhancing anti-osteoporotic effect of Vi. Thin layer dispersion method was employed to prepare Vi-MMs, and then the optimal prescription was optimized by the orthogonal design-response surface method, wherein encapsulation efficiency (EE) was used as optimizing index. The physical properties of Vi-MMs such as appearance morphology, particle size, and zeta potential were also characterized. We further analyzed the in-vitro release of Vi and Vi-MMs in three media and investigated the pharmacokinetics of Vi and Vi-MMs in rats. Anti-osteoporotic activity of Vi and Vi-MMs was assessed by establishing a zebrafish osteoporosis model with prednisone. Drug loading, EE, particle size and zeta potential of the optimized Vi-MMs were 8.58 ± 0.13%, 93.86 ± 1.79%, 20.41 ± 0.64 nm and −10 ± 0.56 mV, respectively. The optimized Vi-MMs were shaped spherically as exhibited by transmission electron microscopic technique, with evident core shell nano-structure, well dispersed. In all three media, the release rate of Vi-MMs was significantly higher than that of free Vi. The oral bioavailability of Vi-MMs was increased by 5.6-fold compared to free Vi. In addition, alleviation of prednisone induced osteoporosis in zebrafish by Vi-MMs further demonstrated good anti-osteoporotic effect. In summary, Vi-MMs exhibited enhanced bioavailability and anti-osteoporotic effect, which is expected to be potential nanocarrier for Vi applications in drug development.
研究领域:
药学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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